A New Formyl Peptide Receptor-1 Antagonist Conjugated Fullerene Nanoparticle for Targeted Treatment of Degenerative Disc Diseases.
Li XiaoRong HuangYi ZhangTinghui LiJun DaiNaga NannapuneniTimothy R ChastanetMatthew ChenFrancis H ShenLi JinHarry C DornXudong LiPublished in: ACS applied materials & interfaces (2019)
Intervertebral disc degeneration associated back pain is the most common cause of disability worldwide; however, no safe and effective treatments have been available. Here, we report a new functionalized nanofullerene conjugated with a peptide that binds specifically to a formyl peptide receptor-1 (FPR-1) expressed on activated macrophages. The new nanoparticle (aka FT-C60) was synthesized by conjugating carboxyl-C60 with the primary amine group of the peptide with a fluorescence dye for easy detection. The new nanoparticle was characterized by X-ray photoelectron spectroscopy, mass spectroscopy, and gel electrophoresis. It possessed effective radical (hydroxyl and superoxide anions) scavenging capabilities in electron paramagnetic resonance spectroscopy. In cultured cells, the nanoparticle FT-C60 demonstrated preferential binding to FPR-1 on activated macrophages and significantly attenuated mRNA expressions of proinflammatory factors including interleukin-6, interleukin-1, tumor necrosis factor-alpha, and cyclooxygenase-2. In vivo animal studies exhibited that a single intravenous injection of FT-C60 effectively alleviated pain in an established mouse model of radiculopathy for up to post-operation day (POD) 12. Ex vivo near-infrared fluorescence imaging of the mouse spine confirmed the targeting property of FT-C60 toward the injured disc on POD 14. Quantitative analysis of histological staining on spine sections showed that nanoparticle FT-C60 dramatically reduced inflammation at the local injury site compared to injury only on POD 7. In summary, we developed a novel targeted nanoparticle for treatment of lumbar radiculopathy by systemic delivery. This is a first-of-its-kind study for developing a novel class of targeted and systemic nanoparticle therapeutics to treat degenerative disc diseases.
Keyphrases
- iron oxide
- high resolution
- cancer therapy
- single molecule
- mouse model
- photodynamic therapy
- rheumatoid arthritis
- induced apoptosis
- multiple sclerosis
- oxidative stress
- endothelial cells
- chronic pain
- low dose
- minimally invasive
- nitric oxide
- ionic liquid
- magnetic resonance imaging
- ultrasound guided
- hydrogen peroxide
- quantum dots
- binding protein
- hyaluronic acid
- smoking cessation
- nitric oxide synthase